A 3 yr old mixed breed dog was presented in December 2017 to a Colorado veterinarian for an 8-h history of lethargy, anorexia, and trembling that had been preceded by 2 days of mild cough. The dog was up to date on vaccines. The owner reported jogging with the dog near prairie dog colonies where a dead prairie dog had been spotted. Physical examination was normal except for hyperthermia (103.1 °F). Complete blood count (CBC) revealed leukocytosis (23,400 cells/μL, RR 5050–16,760 cells/μL) with neutrophilia (18,920 cells/μL, RR 2.6–11.0 × 103 cells/μL). Serum biochemistry analysis found mild elevations in ALT (145 IU/L, RR 10–125 U/L) and GGT (17 IU/L, RR 0–11 IU/L). Concerns for canine infectious respiratory disease complex agents, bacterial hepatitis, leptospirosis, plague, or another infectious etiology were raised. Hospitalization for supportive care, WITNESS Lepto antibody testa, and plague screening were declined by the owner in favor of subcutaneous fluids (25 mL/kg once), maropitant citrate (1 mg/kg SQ once), and amoxicillin/clavulonic acid (17.8 mg/kg PO Q12 h for 7 days) and instructions to recheck with the primary veterinarian in 2–4 days. The next day, the dog returned with progressive lethargy, anorexia, and hemoptysis. Physical examination revealed worsening hyperthermia (104.5 °F), dehydration, and increased bronchovesicular sounds; no cough was noted or elicited. Thoracic radiographs, PT/aPTT, and leptospirosis testing were declined in favor of referral to the Colorado State University Veterinary Teaching Hospital (VTH).
On presentation to the VTH (Day 0), the dog was febrile (105.1 °F), tachypneic (72 brpm) with normal lung sounds, and had a prolonged capillary refill time (3 s). Venous blood gas revealed a metabolic acidosis: pH 7.294 (RR 7.33–7.45), cHCO3 14.0 mEq/L (RR 17–27 mEq/L), hyperlactatemia 3.2 mmol/L (RR 0.20–1.44 mmol/L). No cough was appreciated. Thoracic Focused Assessment with Sonogram for Trauma (T-FAST) for detection of pleural and pericardial effusion was negative. Repeat CBC found moderate neutropenia (1700 cells/μL, RR 2600-11,000 cells/μL) with bands (200 cells/μL, RR 0–200 cells/μL) and moderate toxic change, lymphopenia (300 cells/μL, RR 1000–4800 cells/μL), and severe thrombocytopenia (48,000 cells/μL, RR 200,000-500,000 cells/μL) with few clumps and a normal MPV (8.6 fL, RR 7.5–14.6 fL). Urinalysis was unremarkable. SNAP 4Dxd for Ehrlichia spp., Anaplasma spp., Borrelia burdorferi C6 antibodies, and heartworm antigen was negative.
Thoracic radiographs showed an alveolar pattern limited to the accessory lung lobe (Fig. 1a and c). This was interpreted as bronchopneumonia, possibly consistent with aspirated or migrating foreign body. This interpretation was supported by the dog’s young age, dolichocephalic confirmation, and frequent outdoor activities that had resulted in a previous episode of grass awn aspiration, according to the owner. The dog was hospitalized overnight with IV fluids, ampicillin sodium/sulbactam sodium (50 mg/kg IV Q8 h), enrofloxacin (10 mg/kg IV Q24 h), maropitant citrate (1 mg/kg IV Q24 h), and nebulization (Q6 h). Coughing became apparent overnight.
On Day 1 of hospitalization, the patient had diffuse harsh lung sounds and hemoptysis. There was mild hypoglycemia (64 mg/dL, RR 70–115 mg/dL) and hypoproteinemia (4.7 g/dL, RR 5.0–7.0 g/dL; hypoalbuminemia 2.5 g/dL, RR 3.0–4.3 g/dL; normoglobulinemia 2.2 g/dL, RR 1.5–3.2 g/dL) as well as moderate hyperbilirubinemia (0.5 mg/dL, RR 0.0–0.2 mg/dL), suspicious for sepsis. Mildly elevated ALP (283 IU/L, RR 15–140 IU/L), moderately elevated creatine kinase (1599 IU/L, RR 50–275 IU/L), mild hypobicarbonatemia (11.4 mEq/L, RR 15–25 mEq/L), and hypocalcemia (8.6 mg/dL, RR 9.0–11.5 mg/dL) were also noted. Coagulation panel was concerning for early disseminated intravascular coagulation due to mild prolongation of aPTT (18.0 s, RR 9.8–13.3 s), high end of normal PT (9.2 s, RR 7.4–9.4 s), elevated fibrin degradation products (5.0 μg/mL, RR 0–4.0 μg/mL), elevated D-dimers (0.48 μg/mL, RR 0.03–0.40 μg/mL), low antithrombin III (79%, RR 104–162%), and elevated quantitative fibrinogen (594 mg/dL; 123–210 mg/dL). Computed tomography scan in preparation for a median sternotomy and lobectomy confirmed a consolidated accessory lung lobe interpreted as consistent with foreign body abscessation, multifocal interstitial and alveolar patterns in the remaining lobes, and sternal, cranial mediastinal, and tracheobronchial lymphadenopathy interpreted as reactive.
Median sternotomy, accessory lung lobectomy, and chest tube placement were performed without complication. At surgery, the accessory lung lobe was diffusely consolidated with multifocal to coalescing well-defined regions of hemorrhage on all surfaces. There were scattered small red foci in all other lobes, likely corresponding to the multifocal interstitial and alveolar patterns noted on imaging, which were interpreted as small sites of atelectasis. Scant serosanguinous effusion was noted. Samples of free fluid and a swab of incised lung surface were submitted for bacterial culture and sensitivity. The accessory lung lobe was submitted for histopathology.
The patient recovered in an oxygen cage (30–40%) with fentanyl (2–5 mcg/kg/hr), ketamine (3 mcg/kg/min), intrathoracic lidocaine (1 mg/kg Q8 h), and intrathoracic bupivacaine (1 mg/kg Q8 h) provided. The chest tube was evacuated routinely. All previous medications were continued. Overnight the patient vomited once, but was normothermic and eupneic with an oxygen index greater than 300.
On the following day (Day 2 of hospitalization), oxygen therapy was discontinued and the chest tube was removed. Oral analgesics (tramadol 50 mg PO Q8 h; gabapentin 100 mg PO Q8 h) replaced ketamine and fentanyl. Overnight, the patient became transiently febrile (up to 104 °F). Mild tachypnea (60 brpm), inspiratory dyspnea, diffuse harsh lung sounds, and right-sided crackles developed. Oxygen therapy (40%) was reinstituted. Ondansetron (0.5 mg/kg IV Q12 h) and pantoprazole (1 mg/kg IV Q12 h) were initiated for inappetence and nausea. Repeat CBC found a resolved neutropenia (9,800 cells/μL, RR 2600-11,000 cells/μL) with moderate toxic changes and no left shift, few reactive lymphocytes, and worsening thrombocytopenia (27,000 cells/μL, RR 200,000-500,000 cells/μL) with absent clumps and evidence of increased production (MPV 20.4 fI, RR 7.5–14.6 fI; moderate giant platelets). Repeat thoracic radiographs (Fig. 1b and d) found a progressive multifocal interstitial pattern in all lobes and pleural fissure lines.
Histopathology was read by a board-certified veterinary pathologist on the afternoon of Day 3 of hospitalization (Fig. 2). The parenchyma was effaced by extensive areas of necrosis and hemorrhage with infiltration by large numbers of neutrophils and fewer foamy alveolar histiocytes. In less severely affected areas, alveolar septae were thickened by edema and fibrin. The pleural surface was lined by a mat of fibrin and degenerate neutrophils. Bacteria were not identified with routine hematoxylin and eosin or in a Gram-stained preparation. A diagnosis of severe suppurative and necrohemorrhagic bronchopneumonia with fibrinopurulent pleuritis was made, consistent with a highly pathogenic bacterial infection. Y. pestis was not specifically considered by the pathologist, due to the lack of intralesional coccobacilli, a typical feature of plague infection [20]. Doxycycline (5 mg/kg IV Q12 h) was added and ampicillin-sulbactam/enrofloxacin continued.
On Day 4 of hospitalization, the dog was normothermic but harsh lung sounds persisted. Tramadol was discontinued and capromorelin (40.2 mg PO Q24 h) and cisapride (5 mg PO Q8 h) were initiated due to inappetence. Due to concerns that additional abscesses may be causing bacteremia, an abdominal ultrasound was performed and was unremarkable. On the night of Day 4, the patient remained stable, showed interest in food, and remained normothermic.
On Day 5, the patient became febrile (103.6 °F to 104.5 °F) and dyspneic with bilaterally severe harsh lung sounds and significant right-sided crackles. Repeat CBC showed worsening neutrophilia (11,600 cells/μL, RR 2600-11,000 cells/μL) with toxic changes, bands (100 cells/μL, RR 0–200 cells/μL), and acanthocytes, consistent with fragmentation injury from DIC. Serum biochemistry panel found worsening hypoproteinemia (3.6 g/dL, RR 5.0–7.0 g/dL; hypoalbuminemia 1.7 g/dL, RR 3.0–4.3 g/dL; normoglobulinemia 1.9 g/dL, RR 1.5–3.2 g/dL), hypocalcemia (7.5 mg/dL, RR 9.0–11.5 mg/dL), and hypomagnesemia (1.4 mg/dL, RR 1.8–2.4 mg/dL) with hypokalemia (3.45 mEq/L, RR 3.9–5.4 mEq/L).
Aerobic culture of lung, sampled intraoperatively, yielded sparse, pure growth of a gram-negative organism, which was initially identified as Yersinia pseudotuberculosis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF). This was considered suspicious when reviewed by a veterinary clinical microbiologist due to the body site (lung) from which the organism was isolated, as well as the inconsistency of Y. pseudotuberculosis with the clinical picture. The bacterial isolate and original lung and pleural fluid swab samples were tested for Y. pestis by real-time PCR and Y. pestis was detected in these samples. Biosecurity measures were implemented throughout the VTH. The owner subsequently elected humane euthanasia.
A limited necropsy was performed by a board-certified veterinary pathologist in a specialized BSL2 necropsy facility. Both lungs were multifocally consolidated, especially the cranial lung lobes. Severely affected areas released large amounts of serosanguineous fluid when incised. Diaphragmatic lung lobes failed to collapse and were moderately to markedly hemorrhagic. Tonsils, submandibular, tracheobronchial and mediastinal lymph nodes were mildly to moderately enlarged and edematous. Samples of the tonsils, lungs, spleen, lymph nodes, small intestine, and kidneys were collected and processed routinely for histologic examination. In addition to diffuse severe necrosuppurative and hemorrhagic pneumonia there was acute moderate necrosuppurative tonsillitis (Fig. 2c). Tonsillar lymphoid follicles showed prominent lymphocytolysis and expansion of interlobular septa by neutrophils. No histologic lesions were present within the spleen, small intestine, or lymph nodes. Y. pestis was detected in a post mortem sample of liver by real-time PCR; tonsil, lung, spleen, lymph node, small intestine, and kidney samples were negative.
Case 2 resulted in potential exposure at the VTH of 116 people including veterinarians, veterinary support staff and laboratory technicians, veterinary students, and volunteers and potential exposure of 46 other animals. No individuals were confirmed to have contracted plague. The public health response and ramifications are reported elsewhere [21].